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首页> 外文期刊>Parasitology >Clarithromycin, a cytochrome P_(450) inhibitor, can reverse mefloquine resistance in Plasmodium yoelii nigeriensis -infected Swiss mice
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Clarithromycin, a cytochrome P_(450) inhibitor, can reverse mefloquine resistance in Plasmodium yoelii nigeriensis -infected Swiss mice

机译：克拉霉素是一种细胞色素P_（450）抑制剂，可以逆转感染了约氏疟原虫的瑞士小鼠的甲氟喹抗性

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During the last 2 decades there have been numerous reports of the emergence of mefloquine resistance in Southeast Asia and nearly 50% resistance is reported in Thailand. A World Health Organization report (2001) considers mefloquine as an important component of ACT (artesunate + mefloquine) which is the first line of treatment for the control of uncomplicated/ multi-drug resistant (MDR) Plasmodium falciparum malaria. In view of the emergence of resistance towards this drug, it is proposed to develop new drug combinations to prolong the protective life of this drug. Prior studies have suggested that mefloquine resistance can be overcome by a variety of agents such as ketoconazole, cyproheptadine, penfluridol, Icajine and NP30. The present investigation reports that clarithromycin (CLTR), a new macrolide, being a potent inhibitor of Cyt. P_(450) 3A4, can exert significant resistance reversal action against mefloquine resistance of plasmodia. Experiments were carried out to find out the curative dose of CLTR against multi-drug resistant P. yoelii nigeriensis. Mefloquine (MFQ) and clarithromycin (CLTR) combinations have been used for the treatment of this MDR parasite. Different dose combinations of these two drugs were given to the infected mice on day 0 (prophylactic) and day 1 with established infection (therapeutic) to see the combined effect of these combinations against the MDR malaria infection. With a dose of 32 mg/kg MFQ and 225 mg/kg CLTR, 100% cure was observed, while in single drug groups, treated with MFQ or CLTR, the cure was zero and 40% respectively. Therapeutically, MFQ and CLTR combinations 32+ 300 mg/kg doses cleared the established parasitaemia on day 10. Single treatment with MFQ or CLTR showed considerable suppression of parasitaemia on day 14 but neither was curative. Follow-up of therapeutically treated mice showed enhanced anti-malarial action as reflected by their 100% clearance of parasitaemia. The present study reveals that CLTR is a usefu...
机译：在过去的20年中，有许多关于甲氟喹抗药性在东南亚出现的报道，泰国报道了近50％的抗药性。世界卫生组织的一份报告（2001年）认为甲氟喹是ACT（青蒿琥酯+甲氟喹）的重要组成部分，这是控制简单/多药耐药（MDR）恶性疟原虫疟疾的第一线治疗方法。考虑到对该药物的耐药性的出现，建议开发新的药物组合以延长该药物的保护寿命。先前的研究表明，甲氟喹的耐药性可以通过多种药物克服，例如酮康唑，赛庚啶，喷氟利多，伊卡因和NP30。本研究报告说，新的大环内酯类药物克拉霉素（CLTR）是有效的Cyt抑制剂。 P_（450）3A4，可以对疟原虫的甲氟喹抗性产生显着的抗性逆转作用。进行实验以找出对抗多药抗药性约氏疟原虫的CLTR的治疗剂量。甲氟喹（MFQ）和克拉霉素（CLTR）的组合已用于治疗这种MDR寄生虫。在感染确定的第0天（预防性）和第1天（治疗性）将这两种药物的不同剂量组合给予感染的小鼠，以观察这些组合对MDR疟疾感染的综合作用。在32 mg / kg MFQ和225 mg / kg CLTR的剂量下，治愈率为100％，而在单药组中，用MFQ或CLTR治疗的治愈率分别为零和40％。在治疗上，第10天，MFQ和CLTR组合使用32+ 300 mg / kg剂量可清除既定的寄生虫血症，单用MFQ或CLTR治疗在第14天可明显抑制寄生虫血症，但均不能治愈。经过治疗的小鼠的随访显示出增强的抗疟疾作用，如其寄生虫血症的100％清除所反映。本研究表明，CLTR是一种有用的...

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